NM_001321142.2:c.585G>T

Variant names:

• chr3-9867266-C-A
• rs1379855911
• NM_001321142.2:c.585G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001321142.2(CIDEC):​c.585G>T​(p.Met195Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CIDEC NM_001321142.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 1 publications found

Genes affected

CIDEC (HGNC:24229): (cell death inducing DFFA like effector c) This gene encodes a member of the cell death-inducing DNA fragmentation factor-like effector family. Members of this family play important roles in apoptosis. The encoded protein promotes lipid droplet formation in adipocytes and may mediate adipocyte apoptosis. This gene is regulated by insulin and its expression is positively correlated with insulin sensitivity. Mutations in this gene may contribute to insulin resistant diabetes. A pseudogene of this gene is located on the short arm of chromosome 3. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

CIDEC Gene-Disease associations (from GenCC):

• CIDEC-related familial partial lipodystrophy

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000308530 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321142.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	NM_001321142.2	MANE Select	c.585G>T	p.Met195Ile	missense	Exon 7 of 7	NP_001308071.1	Q96AQ7-1
	CIDEC	NM_001199623.2		c.624G>T	p.Met208Ile	missense	Exon 6 of 6	NP_001186552.1	A0A0A0MRY9
	CIDEC	NM_001199551.2		c.615G>T	p.Met205Ile	missense	Exon 7 of 7	NP_001186480.1	Q96AQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.585G>T	p.Met195Ile	missense	Exon 7 of 7	ENSP00000338642.2	Q96AQ7-1
	CIDEC	ENST00000383817.5	TSL:1	c.624G>T	p.Met208Ile	missense	Exon 6 of 6	ENSP00000373328.2	A0A0A0MRY9
	CIDEC	ENST00000455015.6	TSL:1	c.363G>T	p.Met121Ile	missense	Exon 6 of 6	ENSP00000392975.1	Q96AQ7-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.58	D
PhyloP100		7.3
PROVEAN	Benign	0.52	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Vest4		0.63
MutPred		0.17		Gain of glycosylation at A80 (P = 0.0351)
MVP		0.47
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.45
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1379855911; hg19: chr3-9908950;